Ligand-coated polymer for biological binding

Lead Research Organisation: Imperial College London
Department Name: Materials

Abstract

Seasonal influenza A causes approximately 500,000 deaths and around 3-5 million cases of severe illness annually worldwide, in particular infants, elderly and more in general immunocompromised patients. On of the main hurdles in finding a long-lasting solution to this problem is the high mutation frequency of the influenza virus. This limits the use of vaccination, and vaccine must be annually readapted to circulating influenza strain mutants, with large economic costs. A similar problem arises for currently available antiviral drugs against influenza, which are becoming inactive against the latest strains. Recently, an alternative approach has been suggested, targeting conserved or inevitable viral structures which must be preserved between strain to sustain normal viral replication. In this regard, an important class of viral inhibitors under intensive study is represented by multivalent constructs displaying sialic acid receptors targeting the hemagglutinin glycoproteins of the influenza virus. In general, it is accepted that the working mechanism of this system relies in creating a competition between sialic acid receptors on the multivalent construct and similar receptors on the cell surface. The rational is that if the virus ligands are saturated by binding with these competing receptors, they cannot be used for binding to the cell surface, hence preventing viral penetration and stopping the replication cycle at its very first step. This simple picture has guided various experimental studies trying to link construct architecture and infectivity, but much has still to be understood. A central question in this regard is how the multivalent construct architecture affects the presentation of its ligand, and how this translates into a decrease in viral infectivity. To answer this question, we aim in this project to use state-of-the-art Monte Carlo simulations with coarse-grained models to provide a microscopic picture for viral inhibition by polymers. These models will provide a quantitative description of our system and we aim to translate their results into useful guidelines for the design and synthesis of novel anti-viral architectures.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509486/1 01/10/2016 30/09/2021
2012492 Studentship EP/N509486/1 09/01/2017 11/09/2018 Alessio Bevilacqua